|
| Disease | Expression site of RGMa | Possible mechanisms | Participants or models | Potential therapeutic target |
|
| MS | (1) Significantly upregulated in active and chronic MS lesions [22, 61]
(2) Plasma RGMa is inversely related to delta EDSS [2, 6] | (1) Mediates immune responses [5, 37, 61–64]
(2) Mediates CNS demyelination [38, 39]
(3) Mediates neurodegeneration and inhibits neurite outgrowth [5, 7, 22, 40]
(4) Inhibits neovascularization [5, 36, 65]
(5) May be involved in BBB dysfunction [43–45, 66] | (1) MS patients [6, 22, 44]
(2) EAE rats [5, 61] | (1) Targeting RGMa can improve functional recovery [22]
(2) Anti-RGMa antibody can promote neurite outgrowth and remyelination [5, 22]
(3) Anti-RGMa antibody can reduce immune responses [5] |
| NMOSD | Unknown | (1) May involve loss of AQP4, GFAP, and astrocytes [8, 46, 67]
(2) May aggravate immune responses [8, 47, 68, 69]
(3) May induce neuronal damage [8, 48, 49] | NMOSD model in rats [8] | Inhibition of RGMa can
(1) delay onset [8]
(2) relieve symptoms [8]
(3) delay progression of NMOSD [8] |
| Ischemic stroke | Upregulated in vascular endothelium and neurons after I/R injury [9, 36] | (1) Inhibits axon growth by phosphorylating CRMP-2 [51]
(2) Might inhibit angiogenesis by downregulating BDNF VEGF, Ang1, and Ang2 [35]
(3) May reduce p-FAK (Tyr397) and VEGF via Neogenin and Unc5b [34]
(4) Might impact LMC status [53]
(5) May be involved in BBB dysfunction via the CDC-42/PAK-1 signal pathway [9] | (1) MCAO patients [53]
(2) I/R injury model in rats [9, 35]
(3) Endothelial cell in vitro [34] | (1) Anti-RGMa antibody or RGMa function-blocking peptide can significantly upregulate BDNF, VEGF, Ang1, and Ang2 [34, 35]
(2) Inhibition of RGMa promotes functional recovery by promoting angiogenesis [35]
(2) RGMa may predict LMC status [53]
(3) Silencing RGMa ameliorates infarct volume, brain edema, and BBB dysfunction [9] |
| SCI | Upregulated around SCI lesion [30, 70] | (1) Inhibits neuronal survival [30]
(2) Activates microglia [21] | (1) Patients with SCI [21]
(2) SCI model in monkey [10, 71]
(3) SCI model in mice [30, 72] | (1) Anti-RGMa antibody can promote axon regeneration, plasticity, motor recovery, and manual dexterity [10, 21, 30, 72]
(2) Anti-RGMa antibody can relieve neuralgia [21] |
| PD | Significantly upregulated in the SN of patients with PD [11, 73] | (1) Induces selective degeneration of dopaminergic neurons in the SN [11, 74]
(2) Activates microglia and astrocyte strongly [11, 74]
(3) May inhibit neuronal survival by activating RhoA [58, 74] | (1) Patients with PD [11, 73]
(2) RGMa can model PD in mouse [11] | (1) Inhibition of RGMa may modify PD [11, 75]
(2) Regulating RGMa-Neogenin may promote cell replacement [74]
(3) Anti-RGMa antibody may offer neuroprotection [74] |
| Seizures | Significantly decreased in epileptic patients and rat models [12, 58, 76] | (1) Partly via the FAK-p120Ras GAP-Ras signaling pathway suppresses MFS [12, 76]
(3) Inhibits hyperexcitability of hippocampal neurons via suppressing NMDAR-mediated currents [58] | (1) Epileptic patients [58]
(2) Pentylenetetrazol rat model [12]
(3) Epileptic rat model [58]
(4) Organotypic slice model [58] | Injection recombinant RGMa to intracerebroventricular or overexpression of RGMa suppresses MFS and seizures [12, 58, 76] |
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